The esophageal cancer cohort of a phase 2 trial of E7389-LF (liposomal formulation of eribulin) + nivolumab.
Authors: Akira Ooki, Sachiko Yamamoto, Hisato Kawakami, Tomoki Makino, Akihito Kawazoe, Toshiki Masuishi, Takahiro Tsushima, Motohiro Hirao, Naoki Takegawa, Kaori Hino, Satoru Iwasa, Hiroki Hara, Naoki Sumiyoshi, Daiko Matsuoka, Yohei Otake, Keisuke Yasuda, Takao Takase, Shuya Takashima, Taro Semba, Takashi Oshima
Journal: Journal of Clinical Oncology (2023)

337 Background: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor, eribulin. Treatment with E7389-LF plus the programmed cell death 1 inhibitor nivolumab may result in an increased antitumor effect through vascular remodeling. The phase 1b part of the open-label Study 120 assessed dosing and safety of E7389-LF combined with nivolumab in patients (pts) with solid tumors; the phase 2 part assessed efficacy and safety in expansion cohorts, including an esophageal cancer (EGC) cohort. Methods: For the EGC cohort in the phase 2 part of Study 120, pts were required to have unresectable, measurable (by RECIST v1.1) EGC lesion(s) that showed progression during or after first-line chemotherapy with no other systemic chemotherapy. The primary objective of the phase 2 part was to assess objective response rate (ORR), with success defined as Bayesian posterior probability over 85% beyond threshold (20%) for best overall response (ie, 9 responders of planned 32 pts enrolled). Secondary objectives included assessment of safety and progression-free survival (PFS). The recommended phase 2 dosing regimen was previously determined to be E7389-LF 2.1 mg/m 2 every 3 weeks (Q3W) plus nivolumab 360 mg Q3W. Tumor assessments were performed by RECIST v1.1 every 6 weeks. All adverse events (AEs) were monitored and recorded. Results: In the EGC cohort, 35 pts were included. Most pts (88.6%) were male, and the median age was 69.0 years (range 47–85). At data cutoff (May 31, 2022), 5 pts (14.3%) were still undergoing treatment. Discontinuations occurred in 30 pts (85.7%)—25 (71.4%) due to disease progression, 4 (11.4%) due to an adverse event, and 1 (2.9%) due to patient preference. ORR with E7389-LF + nivolumab was 22.9% (95% CI 10.4–40.1) and the disease control rate (DCR) was 62.9% (95% CI 44.9–78.5). Median PFS was 2.81 months (95% CI 1.31–4.17) and the 6-month PFS rate was 20.2% (95% CI 8.7–35.0). Median OS was not reached (95% CI 6.54–not estimable), and the 6-month OS rate was 71.4% (95% CI 53.4–83.5). Treatment-related treatment-emergent (TE) AEs of any grade and of grade ≥3 occurred in 94.3% and 80.0% of pts, respectively. The most common treatment-related TEAEs of any grade were neutropenia (65.7%), leukopenia (57.1%), and decreased appetite (45.7%). The most common treatment-related TEAEs of grade ≥3 were neutropenia (54.3%), leukopenia (34.3%), and febrile neutropenia (22.9%). TEAEs led to dose reduction of E7389-LF in 17 pts (48.6%). TEAEs led to withdrawal of either E7389-LF or nivolumab in 5 pts (14.3%): pneumonia (n=2), traumatic hemothorax (n=1), acute kidney injury (n=1), and pneumonitis (n=1). Conclusions: E7389-LF combined with nivolumab showed an ORR of 22.9% in pts with EGC. Despite this modest ORR, the DCR of 62.9% was notable. No new safety signals were observed compared to the known profiles of each monotherapy. Clinical trial information: NCT04078295 .